POS0301 STRUCTURAL OUTCOMES IN THE SACROILIAC JOINT AFTER IXEKIZUMAB TREATMENT FOR 16 WEEKS IN PATIENTS WITH ACTIVE NON‑RADIOGRAPHIC AXIAL SPONDYLOARTHRITIS STRATIFIED BY GENDER, HLA-B27, AND BASELINE MRI INFLAMMATION
Authors: W. P. Maksymowych, X. Baraliakos, R. G. Lambert, R. B. M. Landewé, D. Sandoval, H. Carlier, J. Lisse, X. LI, M. Hojnik, M. Østergaard
Journal: Annals of the Rheumatic Diseases (2022)

Background Ixekizumab (IXE) has demonstrated clinical efficacy in patients with active non-radiographic axial spondyloarthritis (nr-axSpA) together with significant repair of structural lesions in the sacroiliac joint (SIJ) on MRI. There is, however, a paucity of data as to which patients may be most responsive. Objectives We aimed to evaluate whether patients’ gender, HLA-B27 status, and presence of MRI inflammation impacted the effect of treatment with IXE versus placebo (PBO) on MRI structural lesions in the SIJ in patients with nr-axSpA. Methods Patients with active nr-axSpA, biologic-naïve (COAST-X, NCT02757352 ) were randomized 1:1:1 to ixekizumab 80 mg every 4 (Q4W) or 2 weeks (Q2W) or PBO. Structural lesions on SIJ MRI were assessed by the Spondyloarthritis Research Consortium of Canada (SPARCC) MRI SIJ structural score (SSS). Treatment comparisons used analysis of covariance based on observed cases. SPARCC SSS subgroup analyses were performed according to baseline gender, HLA-B27 status, and SPARCC MRI SIJ bone marrow oedema (BME) &lt;4 and ≥4 subgroups, which reflects a definite MRI for inflammation in the SIJ typical of axSpA. Results Of 303 randomized patients, 266 patients (Q4W: n=85, Q2W: n=91, PBO: n=90) had an MRI scan at baseline and week 16. At baseline, SPARCC scores were consistently higher in males, and mostly higher in HLA-B27 and BME≥4 positive subgroups. Significant differences between patients treated with IXE versus PBO were observed for male patients, HLA-B27 positives, and those with baseline SPARCC BME ≥4. Numerically similar changes were observed in female patients, patients with negative HLA-B27, and patients with SPARCC BME&lt;4, though not statistically significant. Conclusion Effects of IXE on structural repair are most evident in males, HLA-B27 positives, and patients with definite MRI inflammation at baseline. Table 1. MRI SIJ Structural Lesion Outcomes. Lesion Analysis PBO IXE Q4W IXE Q2W Male (n=39) Female (n=51) Male (n=44) Female (n=41) Male (n=43) Female (n=48) Erosion BL mean 5·167 1·980 3·545 2·817 3·523 2·594 LS mean CFB (SE) 0·51 (0·20) -0·11 (0·17) -0·63 (0·18) -0·11 (0·19) -0·51 (0·18) -0·32 (0·17) P value vs PBO NA NA p&lt;0·001 p&gt;0·99 p&lt;0·001 p=0·37 Fat BL mean 2·051 0·912 2·091 1·293 1·465 0·677 LS mean CFB (SE) -0·02 (0·09) -0·03 (0·08) 0·29 (0·08) 0·03 (0·08) 0·21 (0·08) 0·04 (0·08) P value vs PBO NA NA p=0·01 p=0·65 p=0·062 p=0·51 Backfill BL mean 1·154 0·167 0·663 0·415 0·791 0·323 LS mean CFB (SE) -0·20 (0·13) 0·01 (0·11) 0·39 (0·12) 0·01 (0·12) 0·34 (0·12) 0·14 (0·11) P value vs PBO NA NA p&lt;0·001 p&gt;0·99 p=0·002 p=0·38 Lesion Analysis HLA-B27+ HLA-B27 - HLA-B27+ HLA-B27 - HLA-B27+ HLA-B27 - (n=64 ) (n=25 ) (n=61 ) (n=23 ) (n=65 ) (n=26 ) Erosion BL mean 3·820 2·100 3·467 2·543 3·515 1·827 LS mean CFB (SE) 0·27 (0·15) -0·10 (0·24) -0·49 (0·15) -0·01 (0·25) -0·50 (0·15) -0·17 (0·24) P value vs PBO NA NA p&lt;0·001 p=0·79 p&lt;0·001 p=0·84 Fat BL mean 1·578 1·020 1·328 2·783 1·285 0·462 LS mean CFB (SE) -0·06 (0·06) -0·06 (0·10) 0·22 (0·06) 0·01 (0·10) 0·13 (0·06) 0·10 (0·10) P value vs PBO NA NA p=0·002 p=0·65 p=0·027 p=0·25 Backfill BL mean 0·742 0·240 0·542 0·565 0·762 0 LS mean CFB (SE) -0·12 (0·10) 0·01 (0·16) 0·28 (0·10) 0 (0·17) 0·27 (0·10) 0·16 (0·16) P value vs PBO NA NA p=0·005 p=0·96 p=0·005 p=0·52 Lesion Analysis BME ≥4 BME &lt;4 BME ≥4 BME &lt;4 BME ≥4 BME &lt;4 (n=40 ) (n=50 ) (n=27 ) (n=58 ) (n=38 ) (n=53 ) Erosion BL mean 4·863 2·160 5·352 2·190 5·276 1·425 LS mean CFB (SE) 0·42 (0·19) -0·06 (0·17) -0·70 (0·23) -0·23 (0·16) -0·71 (0·20) -0·19 (0·17) P value vs PBO NA NA p&lt;0·001 p=0·47 p&lt;0·001 p=0·57 Fat BL mean 0·775 1·910 1·926 1·603 1·671 0·604 LS mean CFB (SE) -0·02 (0·08) -0·02 (0·07) 0·54 (0·10) -0·01 (0·07) 0·28 (0·08) 0·01 (0·07) P value vs PBO NA NA p&lt;0·001 p=0·90 p=0·013 p=0·74 Backfill BL mean 0·750 0·470 1·019 0·328 0·763 0·387 LS mean CFB (SE) -0·21 (0·12) 0·01 (0·11) 0·41 (0·15) 0·11 (0·10) 0·49 (0·13) 0·05 (0·11) P value vs PBO NA NA p=0·002 p=0·52 p&lt;0·001 p=0·80 CFB=change from BL. BL=baseline, LS=least squares. Acknowledgements Study was sponsored by Eli Lilly and Company Disclosure of Interests Walter P Maksymowych Speakers bureau: AbbVie, Janssen, Novartis, Pfizer, and UCB, Consultant of: AbbVie, Boehringer Ingelheim, Celgene, Eli Lilly and Company, Galapagos, Janssen, Novartis, Pfizer, and UCB and is Chief Medical Officer of CARE Arthritis Ltd, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB, Xenofon Baraliakos Grant/research support from: Abbvie, Amgen, BMS, Chugai, Galapagos, Gilead, Eli Lilly and Company, MSD, Novartis, Pfizer, Roche, Sandoz, and UCB, Robert G Lambert Consultant of: CARE Arthritis, Image Analysis Group, Parexel, and Pfizer, Robert B.M. Landewé Consultant of: AbbVie, Astra-Zeneca, Bristol Myers Squibb, Celgene, Eli Lilly and Company, Janssen, Gilead, Galapagos, Glaxo-Smith-Kline, Novartis, Pfizer, UCB, Grant/research support from: AbbVie, Novartis, Pfizer, and UCB; and is director of Imaging Rheumatology BV, which is a registered company under Dutch Law, David Sandoval Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Hilde Carlier Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Jeffrey Lisse Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Xiaoqi Li Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maja Hojnik Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Mikkel Østergaard Speakers bureau: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly and Company, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Consultant of: AbbVie, BMS, Boehringer-Ingelheim, Celgene, Eli Lilly and Company, Hospira, Janssen, Merck, Novartis, Novo, Orion, Pfizer, Regeneron, Roche, Sandoz, Sanofi, and UCB, Grant/research support from: AbbVie, BMS, Merck, Celgene, and Novartis